Measurement of histaminase activity in fine needle biopsy aspirates of thyroid indicated that such a measurement provided a reliable and simple test for medullary carcinoma of the thyroid. The enzyme was present in high levels in aspirates drawn from this tumor but not in those drawn from other thyroid tumors or normal thyroid tissue. Studies in 17 patients with mastocytosis, basophilic leukemia, gastric carcinoma and cold-induced urticaria showed a general correlation in plasma histamine levels, urine histamine excretion and symptoms. A urine excretion of greater than 300 micrograms/24 hr (normal 17 micrograms) was accompanied by detectable levels of histamine in plasma and a high basal gastric secretion. Patients with values less than 300 micrograms/24 hr $ had no detectable histamine in plasma, normal gastric secretion but had other symptoms associated with histamine release, such as pruritus, flushing, etc. Although patients with mastocytosis had elevated urine histamine, the values were lower than those with basophilic leukemia. This was attributed to 1) more immediate access of histamine in the basophil to the blood stream and 2) more rapid turnover of histamine in basophils than in the tissue mast cell.